Anti-lipid A monoclonal antibodies alter human endothelial cell ICAM-1 expression in vitro.

Two murine anti-lipid A MAbs (A78S1 and A523), which were protective in a rat model of neonatal endotoxin shock (Goto, M, Zeller WP, Hurley RM, Jong JS, Lee C-H: Prophylaxis and treatment of newborn endotoxic shock with anti-lipid A monoclonal antibodies. Circ Shock 35:60-64, 1991), were tested for their effects on lipid A-induced ICAM-1 expression by cultured human umbilical vein endothelial cells (HUVEC). In the presence of 5% fetal bovine serum, lipid A-induced ICAM-1 expression, as measured by radioimmunoassay following 18 h incubation, was enhanced by A78S1 at lower concentrations (.02-.2 micrograms/ mL) but was inhibited at concentrations of 20 micrograms/mL or greater. Its control immunoglobulin, purified nonspecific IgG2b, enhanced the lipid A-stimulated ICAM expression at all concentrations tested. Neither MAb A523 nor its control immunoglobulin, purified nonspecific IgM, had effects on the lipid A-stimulated ICAM-1 by HUVEC. Although A78S1 and A523 had no direct effects, the control immunoglobulins marginally stimulated ICAM-1 activity at their highest concentrations (possibly due to the presence of endotoxin). Furthermore, in serum-free medium all of the immunoglobulins dose-dependently stimulated ICAM-1 expression. These results demonstrate that anti-lipid A MAbs and other immunoglobulins can exhibit variable effects on unstimulated or lipid A-stimulated ICAM-1 expression by HUVEC depending upon the presence of serum, their concentration, immunoglobulin subclass, or epitope specificity.